Trans-hydrometalation of alkynes by a combination of InCl3 and DIBAL-H: One-pot access to functionalized (Z)-alkenes

Article abstract of DOI:10.1021/ol026401w

(equation presented) Triethylborane-induced hydrometalation of alkynes proceeds in an anti manner to afford the corresponding (Z)-alkenylmetal compounds stereoselectively, where dichloroindium hydride would play a key role. A variety of functional groups including hydroxy, carbonyl, and carboxy groups were tolerant under the reaction conditions. Following iodolysis and cross-coupling reaction of the (Z)-alkenylmetal species show the usefulness of this strategy.

Full text of DOI:10.1021/ol026401w

ORGANIC
LETTERS
2
002
Vol. 4, No. 17
993-2995
Trans-Hydrometalation of Alkynes by a
2
Combination of InCl and DIBAL-H:
3
One-Pot Access to Functionalized
(Z)-Alkenes
Kazuaki Takami, Hideki Yorimitsu, and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto 606-8501, Japan
oshima@fm1.kuic.kyoto-u.ac.jp
Received June 21, 2002
ABSTRACT
Triethylborane-induced hydrometalation of alkynes proceeds in an anti manner to afford the corresponding (Z)-alkenylmetal compounds
stereoselectively, where dichloroindium hydride would play a key role. A variety of functional groups including hydroxy, carbonyl, and carboxy
groups were tolerant under the reaction conditions. Following iodolysis and cross-coupling reaction of the (Z)-alkenylmetal species show the
usefulness of this strategy.
Alkenylmetals are versatile reagents in organic synthesis.
Hydrometalation of alkyne is a promising way to prepare
an alkenylmetal. However, hydrometalation usually affords
ibility with a variety of functional groups. Transition metal-
catalyzed hydrosilylation also mainly yields (E)-alkenyl-
5
silane. Very recently, hydrometalation reactions affording
6
(E)-alkenylmetal reagents. Hydroboration of alkyne always
(Z)-alkenylmetals were reported. However, operationally
proceeds in a syn fashion to provide (E)-alkenylborane.
Preparation of a (Z)-alkenylborane reagent, starting from
alkyne, usually requires multistep synthesis. Moreover,
simple and mild procedures for tailored preparation of (Z)-
alkenylmetal species from alkyne are very limited.
Herein we report a novel access to a (Z)-alkenylmetal
reagent by a combination of indium trichloride and diisobu-
1
protection of hydroxy and carboxy groups is necessary in
2
conducting hydroboration. Hydrostannylation of alkyne is
(
4) (a) Nozaki, K.; Oshima, K.; Utimoto, K. J. Am. Chem. Soc. 1987,
09, 2547-2548. (b) Corey, E.; Ulrich, P.; Fitzpatrick, J. M. J. Am. Chem.
Soc. 1976, 98, 222.
5) (a) Hiyama, T.; Kusumoto, T. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 8, p
63. (b) Ojima, I. In The Chemistry of Organic Silicon Compounds; Patai,
also an efficient method to prepare a vinylic metal. However,
1
3
4
both palladium-catalyzed and radical hydrostannylations
afford (E)-alkenylstannanes as a sole or major product,
although the reactions are attractive as a result of compat-
(
7
S., Rappoport, Z., Eds.; John Wiley: New York, 1989, p 1479.
(
1) (a) Brown, H. C.; Imai, T. Organometallics 1984, 3, 1392-1395.
b) Negishi, E.; Williams, R. M.; Lew, G.; Yoshida, T. J. Organomet. Chem.
975, 92, C4-C6. (c) Campbell, J. B., Jr.; Molander, G. A. J. Organomet.
(6) Rhodium-catalyzed hydroboration, (a) Ohmura, T.; Yamamoto, Y.;
Miyaura, N. J. Am. Chem. Soc. 2000, 122, 4990-4991. Radical hydrostan-
nylation, (b) Nakamura, E.; Machii, D.; Inubushi, T. J. Am. Chem. Soc.
1989, 111, 6849-6850. Rhodium-catalyzed hydrosilylation, (c) Mori, A.;
Takahisa, E.; Kajiro, H.; Hirabayashi, K.; Nishihara, Y.; Hiyama, T. Chem.
Lett. 1998, 443-444. Ruthenium-catalyzed hydrosilylation, (d) Na, Y.;
Chang, S. Org. Lett. 2000, 2, 1887-1889. (e) Trost, B. M.; Ball, Z. T. J.
Am. Chem. Soc. 2001, 123, 12726-12727. Lewis acid-mediated synthesis
of (Z)-alkenylsilanes and -stannanes, (f) Asao, N.; Liu, J.-X.; Sudo, T.;
Yamamoto, Y. J. Org. Chem. 1996, 61, 4568-4571. (g) Sudo, T.; Asao,
N.; Gevorgyan, V.; Yamamoto, Y. J. Org. Chem. 1999, 64, 2494-2499.
(h) Asao, N.; Yamamoto, Y. Bull. Chem. Soc. Jpn. 2000, 73, 1071-1087.
(
1
Chem. 1978, 156, 71-79. (d) Srebnik, M.; Bhat, N. G.; Brown, H. C.
Tetrahedron Lett. 1988, 29, 2635-2638. (e) Deloux, L.; Srebnik, M. J.
Org. Chem. 1994, 59, 6871-6873. (f) Takahashi, K.; Takagi, J.; Ishiyama,
T.; Miyaura, N. Chem. Lett. 2000, 126-127.
(
2) (a) Davies A. G. Organotin Chemistry; VCH: Weinheim, 1997,
Chapters 3.4 and 6.3. (b) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986,
5, 508-524.
3) Ichinose, Y.; Oda, H.; Oshima, K.; Utimoto, K. Bull. Chem. Soc.
Jpn. 1987, 60, 3468-3470.
2
(
1
0.1021/ol026401w CCC: $22.00 © 2002 American Chemical Society
Published on Web 07/23/2002

tylaluminum hydride (DIBAL-H). Treatment of InCl
3
(1.35
A variety of alkynes were subjected to the hydroindation
reaction and following iodolysis (Table 1). Noteworthy is
mmol) in THF with DIBAL-H (1.30 mmol) at 0 °C yielded
7
2
dichloroindium hydride (HInCl ). 1-Dodecyne (1.0 mmol)
and a catalytic amount of triethylborane (0.20 mmol) as a
8
radical initiator were added to the solution at -78 °C. The
Table 1. Triethylborane-Induced Hydroindation of Alkynes
Followed by Iodolysis
resulting solution was stirred for 2.5 h at the same temper-
ature. Acidic workup followed by silica gel column purifica-
tion provided 1-dodecene quantitatively (Scheme 1). Without
entry
1
R
2
yield/%
E/Za
Scheme 1
1
2b
3
4
1a
1a
1b
1c
1d
1e
1f
PhCH2O(CH2)3
PhCH2O(CH2)3
C2H5O2C(CH2)6
HO(CH2)4
2a
2a
2b
2c
2d
2e
2f
79
91
99
78
57
73
98
74
99
1/99
2/98
<1/99
<1/99
<1/99
<1/99
3/97
5
6
7
8
HOCH2
n-C4H9CO(CH2)6
HO2C(CH2)6
CH2dCH(CH2)8
Ph
1g
1h
2g
2h
1/99
7/93
9b
triethylborane, 1-dodecene was produced in only 34% yield.9
Furthermore, 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)
inhibited the reaction (0.2 equiv, 48%; 0.4 equiv, 10%).
These observations suggest that the reaction would involve
a radical mechanism. The reduction of 1-dodecyne proceeded
in an anti fashion to yield (Z)-1-dodecenylmetal. Quenching
with DCl yielded (Z)-1-deuterio-1-dodecene exclusively
a
Determined by H NMR. b The reaction was performed at -40 °C.
1
the fact that many functional groups including hydroxy,
carbonyl, and carboxy groups did not interfere with the
reaction (entries 3-7). The hydroindation proceeded much
faster at the alkynyl moiety than at the alkenyl group to yield
iodo diene selectively starting from enyne (entry 8). Addition
to phenylacetylene yielded a mixture of E/Z isomers with
slightly lower selectivity (7/93, entry 9). No desired product
was obtained in the reaction of trimethylsilylacetylene.
Interestingly, hydroindation of enyne 3 at 25 °C afforded
(96% D, E/Z < 1/99). Iodolysis of the reaction mixture also
afforded the corresponding (Z)-isomer selectively in 92%
1
0
yield.
We assume that the reaction would proceed via a radical
addition of indium hydride reagent across a carbon-carbon
triple bond.11 The selectivity is mostly due to the low
reactivity of dichloroindium radical toward (Z)-alkenylindium
dichloride that is initially formed.12 If the further addition
occurs, diindium species is formed, which leads to isomer-
ization of the (Z)-alkenylindium compound into its (E)-form
via an addition-elimination sequence.
4
in 30% yield (Scheme 2). The formation of 4 was highly
Scheme 2
1
(
7) H NMR measurements revealed the formation of HInCl2. The
hydride attached to aluminum of DIBAL-H appeared at δ 3.8 ppm (broad)
in THF-d8. A new broad signal (δ 6.8 ppm) was observed after treatment
of InCl3 with DIBAL-H. Baba reported that hydride of HInCl2, prepared
from InCl3 and n-Bu3SnH, appeared at δ 6.5 ppm. See, Miyai, T.; Inoue,
K.; Yasuda, M.; Shibata, I.; Baba, A. Tetrahedron Lett. 1998, 39, 1929-
1
932. However, Baba’s HInCl2 did not add to alkynes. The reason for the
different reactivity is not clear. Diisobutylaluminum chloride might
coordinate to HInCl2, thereby changing the reactivity.
(
8) (a) Oshima, K.; Utimoto, K. J. Synth. Org. Chem. Jpn. 1989, 47,
0-52. (b) Yorimitsu, H.; Oshima, K. In Radicals in Organic Synthesis;
Renaud, P., Sibi, M. P., Eds.; Wiley-VCH: Weinheim, 2001, Chapter 1.2.
c) Ollivier, C.; Renaud, P. Chem. ReV. 2001, 101, 3415-3434.
9) Indium hydride spontaneously induces radical reaction. See ref 11.
4
(
(
suggestive of a radical mechanism for this hydroindation
reaction. Namely, radical addition of indium-centered radical
to the alkyne moiety of 3 would produce vinyl radical 5.
Following 5-exo ring closure mostly constructs methylene-
cyclopentane skeleton.
Moreover, some organoaluminum compounds can initiate a radical reaction.
See, Chakraborty, A.; Marek, I. Chem. Commun. 1999, 2375-2376.
(
10) The hydroindation reaction at 0 °C, -10 °C, and -40 °C yielded
a mixture of stereoisomers (E/Z ) 20/80, 6/94, and 3/97, respectively) after
iodolysis.
(
11) Reduction of organic halides via a radical process was recently
reported. Inoue, K.; Sawada, A.; Shibata, I.; Baba, A. J. Am. Chem. Soc.
002, 124, 906-907.
12) (a) Ichinose, Y.; Nozaki, K.; Wakamatsu, K.; Oshima, K.; Utimoto,
Increasing attention has been paid to the cross-coupling
2
13
reaction of organic halides with organoindiums. However,
(
K. Tetrahedron Lett. 1987, 28, 3709-3712. (b) Nozaki, K.; Ichinose, Y.;
Wakamatsu, K.; Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn. 1990, 63,
(13) (a) P e´ rez, I.; P e´ rez Sestelo, J.; Sarandeses, L. A. Org. Lett. 1999,
1, 1267-1269. (b) Gelman, D.; Schumann, H.; Blum, J. Tetrahedron Lett.
2000, 41, 7555-7558. (c) Fujiwara, N.; Yamamoto, Y. J. Org. Chem. 1999,
64, 4095-4101. (d) Hirashita, T.; Yamamura, H.; Kawai, M.; Araki, S.
Chem. Commun. 2001, 387-388. (e) P e´ rez, I.; P e´ rez Sestelo, J.; Sarandeses,
2
268-2272. (c) Taniguchi, M.; Nozaki, K.; Miura, K.; Wakamatsu, K.;
Oshima, K.; Utimoto, K. Bull. Chem. Soc. Jpn. 1992, 65, 349-354. (d)
Chatgilialoglu, C.; Ballestri, M.; Ferreri, C.; Vecchi, D. J. Org. Chem. 1995,
6
0, 3826-3831.
2994
Org. Lett., Vol. 4, No. 17, 2002

optimization of the reaction conditions, a DMI (1,3-dimeth-
ylimidazolidin-2-one)/THF mixed solvent system proved to
be effective to obtain coupling products. DMI (3 mL) was
added to a THF solution of the (Z)-1-octenylindium reagent
prepared as aforementioned. Iodobenzene (1.0 mmol) and
palladium-trifurylphosphine complex (0.5 mol %)14 were
then added. Heating the mixture at 66 °C for 30 min afforded
â-hexylstyrene (7a, E/Z ) 5/95) in 94% yield (Table 2).
Various combinations of alkynes and aryl iodides were
examined as summarized in Table 2. High stereoselectivity
was accomplished in each case. Several functional groups
were compatible in this one-pot reaction. In particular,
coupling of 5-hexyn-1-ol with 3-iodoanisole represents the
usefulness of the present strategy (entry 13).
In summary, triethylborane-induced hydroindation of
alkyne proceeds in an anti manner to afford the corresponding
(Z)-alkenylindium species. This method allows us to employ
unprotected alkyne as a (Z)-alkenylmetal precursor and to
synthesize functionalized (Z)-alkenyl iodide and (Z)-alkene
in one pot.
Table 2. One-Pot Hydroindation/Coupling Reaction for
Synthesis of (Z)-Alkenes
entry
1
R1
R2
7
yield/% E/Za
1
2
3
4
5
6
7
8
9
1
1
1
1
1i n-C6H13
1i n-C6H13
1i n-C6H13
1i n-C6H13
1i n-C6H13
1i n-C6H13
1i n-C6H13
1b C2H5O2C(CH2)6
H
2-NO2
4-NO2
2-CO2-n-C4H9 7d
3-OCH3 7e
2-iodopyridine 7f
3-OH
H
7a
7b
7c
94
98
99
91
89
75
46
92
99
70
90
99
99
5/95
5/95
5/95
5/95
5/95b
3/97b
7g
7h
7i
7j
7k
7l
1/99
3/97
5/95
2/98
5/95
2/98
3/97b
1b C2H5O2C(CH2)6 4-NO2
0
1
2
3
1j TBSO(CH2)3c
1j TBSO(CH2)3c
1c HO(CH2)4
H
4-NO2
4-NO2
3-OCH3
1c HO(CH2)4
7m
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research (Nos. 12305058 and 10208208)
from the Ministry of Education, Culture, Sports, Science and
Technology, Government of Japan.
a
1
b
Determined by H NMR. Hydroindation was performed at -40 °C.
c
TBS ) t-BuMe2Si
most organoindium reagents used were prepared from indium
trichloride and the corresponding organolithium or -magne-
sium reagents. With this protocol to prepare alkenylindium
compounds in hand, we investigated cross-coupling reaction
of aryl halides with alkenylindiums in one pot. After
Supporting Information Available: Detailed experi-
mental procedures and characterization of new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL026401W
L. A. J. Am. Chem. Soc. 2001, 123, 4155-4160. (f) Lee, P. H.; Sung, S.;
Lee, K. Org. Lett. 2001, 3, 3201-3204. (g) Takami, K.; Yorimitsu, H.;
Shinokubo, H.; Matsubara, S.; Oshima, K. Org. Lett. 2001, 3, 1997-1999.
(14) The palladium catalyst was prepared from Pd2(dba)3‚CHCl3 (0.0025
mmol) and P(2-furyl)3 (0.015 mmol) in THF (1.0 mL) in another flask.
Org. Lett., Vol. 4, No. 17, 2002
2995